Appendices

Appendix I: Baseline characteristics of Asian participants from RE-LY trial versus anticoagulation clinic patients from Singapore General Hospital

RE-LY / Hospital database
n (warfarin patients) / 926 / 122
Mean TTR, % / 56.5 / 64.5
Mean age, years / 68.0 / 71.9
Male gender, % / 63.8 / 56.9
CHADS2, mean (SD) / 2.2 (1.1) / 3.2 (1.4)
HAS-BLED, mean (SD) / – / 2.3 (0.9)

RE-LY: Randomized Evaluation of Long-Term Anticoagulation Therapy

TTR: Time in therapeutic range

Appendix II: Parameterization of distributions for probabilistic sensitivity analysis

Variable clinical input / Distribution (parameters)
Intracranial hemorrhage (3 monthly)
Rate of Intracranial hemorrhage
Probability of recurrent intracranial hemorrhage
Probability of death from intracranial hemorrhage
Extracranial hemorrhage (3 monthly)
Rate of extracranial hemorrhage (ACC<70%)
Rate of extracranial hemorrhage (ACC≥70%)
Probability of recurrent extracranial hemorrhage
Probability of death from extracranial hemorrhage
Ischemic stroke (3 monthly)
Rate of ischemic stroke
Probability of recurrent ischemic stroke
Probability of death from ischemic stroke
Myocardial infarction (3 monthly)
Rate of myocardial infarction
Rate of recurrent myocardial infarction
Probability of death from myocardial infarction / Log-normal (u, sigma)
-7.849, 3.123 × 10-5
-5.257, 1.302 × 10-3
-1.466, 1.353 × 10-2
Log-normal (u, sigma)
-5.741, 2.364 × 10-3
-5.928, 1.982 × 10-3
-2.371, 1.196 × 10-2
-2.976, 2.282 × 10-2
Log-normal (u, sigma)
-6.660, 5.658 × 10-5
-3.357, 2.082 × 10-3
-3.380, 3.322 × 10-3
Log-normal (u, sigma)
-5.991, 7.905× 10-5
-5.015, 4.592 × 10-4
-2.419, 3.087 × 10-3
Utility
Well with AF
Extracranial hemorrhage
Intracranial hemorrhage
Ischemic stroke
Myocardial infarction
Death
Age related decrement (per year) / Beta (alpha, beta)
4.931, 0.807
6.555, 2.685
7.855, 4.057
11.844, 11.563
7.112, 3.225
–
–
Cost (patient’s perspective), SG$
Pharmacist consult (per session)
Physician consult (per session)
INR test (per test)
Outpatient rehabilitation (per session)
Extracranial hemorrhage (per event)
Intracranial hemorrhage (per event)
Ischemic stroke (per event)
Myocardial Infarction (per event)
Transport (per round trip)
Cost (healthcare provider’s perspective), SG$
Pharmacist consult (per session)
Physician consult (per session)
INR test (per test)
Outpatient rehabilitation (per session)
Extracranial hemorrhage (per event)
Intracranial hemorrhage (per event)
Ischemic stroke (per event)
Myocardial Infarction (per event)
Frequency (three monthly)
Physician consults for ACC TTR<70%
Pharmacist consults for ACC TTR<70%
Physician consults for ACC TTR≥70%
Pharmacist consults for ACC TTR≥70%
Physician consults for UC TTR<70%
Factor for physician consults for UC TTR≥70%
Outpatient rehabilitation (weekly)
Government subsidy to healthcare institute (proportion of total cost)
Relative risk
Ischemic stroke (ACC vs. UC)
Ischemic stroke (per decade)
Ischemic stroke (ACC TTR<70% vs. ACC TTR≥70%)
Myocardial infarction (ACC vs. UC)
Myocardial infarction (per decade)
Intracranial hemorrhage (ACC vs. UC)
Intracranial hemorrhage (warfarin vs. antiplatelet)
Intracranial hemorrhage (per decade)
Extracranial hemorrhage (ACC vs. UC)
Extracranial hemorrhage (per decade)
Reduction for ischemic stroke (warfarin vs. antiplatelet)
Reduction for myocardial infarction (warfarin vs. non-warfarin anticoagulants)
Discount rate (annual) / Gamma (alpha, lambda)
–
–
–
–
0.411, 6.600 × 10-5
0.684, 5.919 × 10-5
0.880, 1.615 × 10-4
25.000, 1.675 × 10-2
0.698, 0.144
Gamma (alpha, lambda)
–
–
–
–
0.494, 2.570 × 10-5
2.333, 8.378 × 10-5
2.729, 3.108 × 10-4
25.000, 3.350 × 10-3
Poisson (lambda)
0.497
1.710
0.367
1.185
1.584
–
–
–
Log-normal (u, sigma)
-0.236, 0.451
–
–
-0.236, 0.451
–
-0.446, 0.656
0.683, 0.531
–
-0.446, 0.656
–
-0.635, 6.887 × 10-2
-
-0.371, 1.378 × 10-1
–

ACC: anticoagulation clinic; UC: usual care; SG$: Singapore dollars; TTR: time in therapeutic range

Appendix III: Validation of model with data of Asian participants from the novel oral anticoagulant trials

Incidence (% per year)
Extracranial hemorrhage / Intracranial hemorrhage / Ischemic stroke / Myocardial infarction
ARISTOTLE / 1.96 / 1.88 / 1.90 / 0.39
Model results / 2.01 / 1.91 / 2.01 / 0.40
ROCKET-AF / 2.68 / 2.46 / 2.24 / 0.99
Model results / 2.62 / 2.62 / 2.18 / 0.87
RE-LY / 2.72 / 1.10 / 2.02 / 0.58
Model results / 2.96 / 0.98 / 1.96 / 0.43
Present study results / 1.36 / 0.39 / 1.48 / 0.68

ARISTOTLE: Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation;
ROCKET-AF: Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation;
RE-LY: Randomized Evaluation of Long-Term Anticoagulation Therapy.